rs863223314

Variant names:

• chr14-50628428-T-TA
• rs863223314
• NM_015915.5:c.1519dupA

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_015915.5(ATL1):​c.1519dupA​(p.Ile507AsnfsTer16) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATL1 NM_015915.5 frameshift
• Clinical Significance: Conflicting classifications of pathogenicity no assertion criteria provided P:2 U:1
• Conservation: PhyloP100: 0.463

Genes affected

ATL1 (HGNC:11231): (atlastin GTPase 1) The protein encoded by this gene is a GTPase and a Golgi body transmembrane protein. The encoded protein can form a homotetramer and has been shown to interact with spastin and with mitogen-activated protein kinase kinase kinase kinase 4. This protein may be involved in axonal maintenance as evidenced by the fact that defects in this gene are a cause of spastic paraplegia type 3. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATL1	NM_015915.5	c.1519dupA	p.Ile507AsnfsTer16	frameshift_variant	Exon 12 of 14	ENST00000358385.12	NP_056999.2
ATL1	NM_001127713.1	c.1519dupA	p.Ile507AsnfsTer40	frameshift_variant	Exon 13 of 14		NP_001121185.1
ATL1	NM_181598.4	c.1519dupA	p.Ile507AsnfsTer40	frameshift_variant	Exon 12 of 13		NP_853629.2
ATL1	XM_047431430.1	c.1519dupA	p.Ile507AsnfsTer16	frameshift_variant	Exon 13 of 15		XP_047287386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATL1	ENST00000358385.12	c.1519dupA	p.Ile507AsnfsTer16	frameshift_variant	Exon 12 of 14	1	NM_015915.5	ENSP00000351155.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:2 Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Hereditary spastic paraplegia 3A Pathogenic:2 Uncertain:1

Dec 24, 2002

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Jan 06, 2016

Inherited Neuropathy Consortium Ii, University Of Miami

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Sep 21, 2010

GeneReviews

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: curation

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs863223314; hg19: chr14-51095146;